Iron absorption and cellular transport: the mobilferrin/paraferritin paradigm.
Dietary inorganic iron is mostly ferric iron. This is solubilized at the acid pH level of the stomach where it chelates mucins and certain dietary constituents to keep them soluble and available for absorption in the more alkaline duodenum. Mucosal uptake of iron is facilitated by a beta 3 integrin and a 56 kDa protein known as mobilferrin. In the cytosol of the absorptive cell, iron is associated with a 520-kDa complex known as paraferritin which contains integrin, mobilferrin, and flavin monooxygenase. This complex serves as a ferrireductase to reduce iron to the ferrous state so that it is available for formation of end products such as heme proteins. The large complex has other constituents, such as beta 2 microglobulin, whose functions remain to be delineated. We postulate that the basolateral membranes of absorptive cells possess both holo-transferrin and apotransferrin receptors that regulate the ingress and egress of cellular iron, respectively. Unlike absorptive cells, nonintestinal cells appear to possess three pathways for uptake of inorganic iron: (1) the classical transferrin-transferrin receptor pathway, (2) the transferrin-associated transferrin receptor independent pathway (TRIP), and (3) the transferrin-independent mobilferrin-integrin pathway (MIP) observed in intestinal absorptive cells. The TRIP is used when transferrin receptors become saturated at physiological concentrations of iron and transferrin. The MIP may only be used efficiently for mucosal uptake of iron and iron-overloaded individuals with fully saturated transferrin. Alternatively, it may facilitate iron uptake from the TRIP after degradation of transferrin near the surface of the cell. However, both transferrin-associated pathways donate iron to a common intracellular iron pathway for ferri-reduction and probably other functions.
Umbreit
J N
JN
USA Cancer Center, University of South Alabama, Mobile 36688, USA.
Conrad
M E
ME
Moore
E G
EG
Latour
L F
LF
D001692:Biological Transport; D002352:Carrier Proteins / Q000502:physiology; D006801:Humans; D007408:Intestinal Absorption; D007422:Intestines / Q000166:cytology; D007501:Iron / Q000493:pharmacokinetics*; D033862:Iron-Binding Proteins
D002352:Carrier Proteins; D033862:Iron-Binding Proteins; C085511:mobilferrin; D007501:Iron